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Pfizer and Astellas Announce Positive Top-Line Results from Phase 3 PROSPER Trial of XTANDI (enzalutamide) in Patients with Non-Metastatic Castration-Resistant Prostate Cancer

On September 14, 2017 Pfizer Inc. (NYSE:PFE) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Yoshihiko Hatanaka, "Astellas") reported that the Phase 3 PROSPER trial evaluating XTANDI (enzalutamide) plus androgen deprivation therapy (ADT) versus ADT alone in patients with non-metastatic (M0) Castration-Resistant Prostate Cancer (CRPC) met its primary endpoint of improved metastasis-free survival (MFS) (Press release, Pfizer, SEP 14, 2017, View Source [SID1234520514]). The preliminary safety analysis of the PROSPER trial appears consistent with the safety profile of XTANDI in previous clinical trials.

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"Many prostate cancer patients who initiate androgen deprivation therapy will experience disease progression illustrated by a rising PSA level, and currently, there are no FDA-approved treatment options for patients with non-metastatic CRPC until they develop confirmed radiographic metastatic disease," said Neal Shore, M.D., director, CPI, Carolina Urologic Research Center.

Based on the results of PROSPER, the companies intend to discuss the data with global health authorities to potentially support expanding the label for XTANDI to cover all patients with CRPC.

"We are delighted with the significant results seen in the PROSPER study, showing that XTANDI plus ADT delayed clinically detectable metastases compared to ADT alone in patients with non-metastatic CRPC whose only sign of underlying disease was a rapidly rising prostate-specific antigen (PSA) level. We look forward to discussing the data with regulatory authorities," said Mace Rothenberg, M.D., chief development officer, Oncology, Pfizer Global Product Development. "XTANDI is already established as a standard of care for men with metastatic CRPC based on the results of prior studies, such as AFFIRM and PREVAIL, which demonstrated that XTANDI delayed disease progression and improved overall survival in men with clinically detectable metastatic disease."

"We want to thank the patients, family members and clinicians who participated in the PROSPER trial and helped advance the scientific understanding of the potential role for XTANDI in this prevalent disease," said Steven Benner, M.D., senior vice president and global therapeutic area head, oncology development, Astellas. "We look forward to further analyzing the detailed efficacy and safety results from PROSPER, and submitting them for presentation at an upcoming major medical meeting."

As part of Pfizer and Astellas’ ongoing commitment to the clinical development of enzalutamide in areas of greatest unmet need, the companies initiated the PROSPER trial to evaluate the potential benefits of XTANDI in men with non-metastatic CRPC, an earlier stage of prostate cancer where there are currently no FDA-approved treatment options. On June 9, 2017, the companies announced an amendment to the PROSPER protocol, which accelerated the clinical trial completion date by two years.

XTANDI is currently approved for the treatment of metastatic CRPC based on clinical data from previous studies that showed a statistically significant overall survival benefit for XTANDI versus placebo in the metastatic CRPC setting. XTANDI has been prescribed to more than 185,000 patients globally since its first approval in 2012.

About PROSPER

The Phase 3 randomized, double-blind, placebo-controlled, multi-national trial enrolled approximately 1,400 patients with non-metastatic castration-resistant prostate cancer (CRPC) at sites in the United States, Canada, Europe, South America and the Asia Pacific region. PROSPER enrolled patients with prostate cancer that had progressed, based on a rising prostate-specific antigen (PSA) level despite androgen deprivation therapy (ADT), but who had no symptoms with no prior or present evidence of metastatic disease. The primary objective of the trial was metastasis-free survival (MFS). MFS is a measure of the amount of time that passes until a cancer can be radiographically detected as having metastasized, or spread, to other parts of the body. The trial evaluated enzalutamide at a dose of 160 mg taken orally once daily plus ADT, versus placebo plus ADT. For more information on the PROSPER trial go to www.clinicaltrials.gov.

XTANDI has not yet been evaluated by the FDA for the treatment of patients with non-metastatic CRPC.

About Non-Metastatic Castration-Resistant Prostate Cancer

According to the American Cancer Society, more than 161,000 men are estimated to be diagnosed with prostate cancer in 2017.[i] Castration-resistant prostate cancer (CRPC) refers to the subset of men whose prostate cancer progresses despite androgen deprivation therapy.[ii] Non-metastatic CRPC means there is no clinically detectable evidence of the cancer spreading to other parts of the body (metastases), and there is a rising prostate-specific antigen (PSA) level.[iii] Many men with non-metastatic CRPC will go on to develop metastatic CRPC.[iv]

About XTANDI (enzalutamide) capsules

XTANDI (enzalutamide) is an androgen receptor inhibitor that blocks multiple steps in the androgen receptor signaling pathway within the tumor cell. In preclinical studies, enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors, and inhibit androgen receptor nuclear translocation and interaction with DNA. The clinical significance of this mechanism of action (MOA) is unknown.

XTANDI is approved by the U.S. Food and Drug Administration for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). Additional ongoing studies, such as the ARCHES trial in metastatic hormone-sensitive prostate cancer and the EMBARK trial in non-metastatic hormone-sensitive prostate cancer, are continuing to evaluate the potential of enzalutamide to help patients in need.

Important Safety Information

Contraindications

XTANDI is not indicated for women. XTANDI can cause fetal harm and potential loss of pregnancy.

Warnings and Precautions

Seizure occurred in 0.5% of patients receiving XTANDI in clinical studies. In a study of patients with predisposing factors, seizures were reported in 2.2% of patients. See section 5.1 of the Prescribing Information for the list of predisposing factors. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) In post approval use, there have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder which can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Adverse Reactions

The most common adverse reactions (≥ 10%) that occurred more commonly (≥ 2% over placebo) in the XTANDI patients from the two placebo-controlled clinical trials were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo. In the bicalutamide-controlled study of chemotherapy-naïve patients, the most common adverse reactions (≥ 10%) reported in XTANDI patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, upper respiratory tract infection, diarrhea, and weight loss.

In the placebo-controlled study of patients taking XTANDI who previously received docetaxel, Grade 3 and higher adverse reactions were reported among 47% of XTANDI patients and 53% of placebo patients. Discontinuations due to adverse events were reported for 16% of XTANDI patients and 18% of placebo patients. In the placebo-controlled study of chemotherapy-naïve patients, Grade 3-4 adverse reactions were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to adverse events were reported for 6% of both study groups. In the bicalutamide-controlled study of chemotherapy-naïve patients, Grade 3-4 adverse reactions were reported in 38.8% of XTANDI patients and 37.6% of bicalutamide patients. Discontinuations due to adverse events were reported for 7.6% of XTANDI patients and 6.3% of bicalutamide patients.

Lab Abnormalities: In the two placebo-controlled trials, Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and 6% of placebo patients (0.5% Grade 3-4). Grade 1-4 thrombocytopenia occurred in 6% of XTANDI patients (0.3% Grade 3-4) and 5% of placebo patients (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of XTANDI patients (0.2% Grade 3-4) and 16% of placebo patients (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of XTANDI patients (0.1% Grade 3-4) and 2% of placebo patients (no Grade 3-4).

Infections: In the study of patients taking XTANDI who previously received docetaxel, 1% of XTANDI patients compared to 0.3% of placebo patients died from infections or sepsis. In the study of chemotherapy-naïve patients, 1 patient in each treatment group (0.1%) had an infection resulting in death.

Falls (including fall-related injuries) occurred in 9% of XTANDI patients and 4% of placebo patients in the two placebo-controlled trials. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in XTANDI patients, and included non-pathologic fractures, joint injuries, and hematomas.

Hypertension occurred in 11% of XTANDI patients and 4% of placebo patients in the two placebo-controlled trials. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of patients in each arm.

Drug Interactions

Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI.

Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

Please see Full Prescribing Information for additional safety information.

SELLAS’ Galinpepimut-S Induces Specific, Robust and Durable Immune Responses in Patients With High-Risk Multiple Myeloma – Correlated With Clinical Benefit

On September 14, 2017 SELLAS Life Sciences Group Ltd. (SELLAS), a privately-held, oncology-focused, clinical stage biopharmaceutical company, reported that its WT1-targeting immuno-oncology (IO) treatment, galinpepimut-S, led to mounting of specific, potent and durable immune responses (IRs) in multiple myeloma (MM) patients (Press release, Sellas Life Sciences, SEP 14, 2017, View Source;Correlated-With-Clinical-Benefit/default.aspx [SID1234520526]).

Galinpepimut-S, is SELLAS’ lead product candidate and is currently expected to enter a pivotal, Phase 3 clinical trial in patients with AML and is also in various development phases in multiple myeloma and ovarian cancer, and additional indications are expected as a monotherapy or in combination with other immuno-oncology agents. The data reported in this release pertain to its ongoing Phase 2 study evaluating galinpepimut-S as a treatment in MM.

In the ongoing Phase 2 study, both the rate (frequency) and potency of the durable IRs in MM patients were correlated with clinical benefit accorded by galinpepimut-S, hereby defined as achievement of cCR/VGPR in patients who completed per protocol immunizations (12 doses). These novel data were presented yesterday, September 13, 2017 , at the Annual Meeting of the Society of Hematologic Oncology (SOHO) in Houston, Texas , USA ( soho2017.com ) at a poster session and the relevant abstract (#MM-252) was published in the September 2017 supplemental issue of the journal Clinical Lymphoma, Myeloma & Leukemia . These IR results considerably expand on previous clinical observations of notable anti-myeloma activity of this innovative IO agent after upfront induction, melphalan conditioning and successful autologous stem cell transplantation (ASCT).

SELLAS’ Phase 2 MM study has enrolled a total of 20 patients who are being monitored long-term. A current median progression-free survival (PFS) of 23.6 months post-ASCT was previously reported in a group of 18 patients, all of whom had evidence of at least minimal residual disease (MRD+) post-ASCT, with 15/18 also having high-risk cytogenetics at baseline. This group represents a population at extremely high risk for progression and poor long-term outcomes, even in the face of post-ASCT maintenance therapy with immunomodulatory drugs (IMiD’s).

Rates of IRs (CD4 and/or CD8) toward any of galinpepimut-S’s individual WT1 peptides (two heteroclitic and four native), as well as a pool of 113 partially overlapping 15-mers spanning the entire length of WT1 (‘all pool’ reactivity) were high at the time of completion of per protocol immunizations, ranging from 72-91%. The rates of immunization against the cognate native epitopes (122A and WT1A) of the two heteroclitic peptides (122A1 and WT1A1) within galinpepimut-S were also high, thus demonstrating the principle of heteroclitic peptide antigenicity. Multivalent IRs (i.e., IRs against more than one WT1 peptide) were detected in up to 66% of patients. IR against WT1 ‘all pool’ peptides denoted multifunctional cross-epitope T-cell reactivity – akin to epitope spreading- and is a hallmark of an effective, cytotoxicity-inducing vaccine. Both the frequency and potency of CD4 IRs against the four native WT1 peptides targeted by galinpepimut-S, as well as ‘all pool’ WT1 antigens, showed a strong positive correlation with indices of clinical benefit (rate of CR/VGPR) at the time of completion of per protocol immunizations. Scientific abstracts describing SELLAS’ findings above will be submitted for presentation in upcoming major medical meetings.

"The results of these immunodynamics assays denote a robust immunobiological foundation for the clinical effect of WT1-targeting active immunization with galinpepimut-S, and suggests key roles of both enduring CD4 activation and emergence of cross-epitopic reactivity for antimyeloma activity with this therapy. The data also support our rationale for planning further studies to expand on our experience with this IO agent," said Guenther Koehne , MD, PhD, Principal Investigator on the trial and Attending Physician, Adult Bone Marrow Transplantation Service at Memorial Sloan Kettering Cancer Center , Associate Professor of Medicine, Weill Cornell Medical College .

Dr. Nicholas Sarlis , MD, PhD, Chief Medical Officer of SELLAS, commented: "The correlations between IR and depth of clinical responses in multiple myeloma patients are both intriguing and original, and firmly establish WT1 as a major actionable target for immunotherapy in plasma cell dyscrasias henceforth."

Dr. Angelos Stergiou , MD, ScD h.c., Vice Chairman and Chief Executive Officer of SELLAS, said: "This new dataset focusing on dissecting the immune mechanisms underlying the marked antimyeloma activity previously documented with galinpepimut-S underscores our steadfast commitment to advance this agent’s clinical development programs, especially in clinical settings of unmet medical need, such as high-risk MRD(+) multiple myeloma after front-line therapy, a space which is currently underserved by standard therapies. These findings further corroborate immune response data from our earlier programs in acute myeloid leukemia (AML) and mesothelioma, where high rates of WT1-specific immunization were seen in conjunction to promising clinical activity signals in these tumor types. Finally, they provide justification for pursuance of future combinatorial approaches with galinpepimut-S, for example with checkpoint inhibitors, especially given the agent’s overall excellent safety profile."

INDEPENDENT DATA MONITORING COMMITTEE RECOMMENDS DISCONTINUATION OF BAVARIAN NORDIC’S PHASE 3 STUDY OF PROSTVAC IN METASTATIC PROSTATE CANCER

On September 14, 2017 Bavarian Nordic A/S (OMX: BAVA, OTC: BVNRY) reported that an independent Data Monitoring Committee (DMCB) has determined, based on a preplanned interim analysis, that continuation of the Phase 3 PROSPECT study of PROSTVAC in patients with metastatic castration-resistant prostate cancer (mCRPC) is futile (Press release, Bavarian Nordic, SEP 14, 2017, View Source [SID1234520525]).

"We are extremely disappointed for patients that this study of PROSTVAC as monotherapy was not successful," said Paul Chaplin, President & Chief Executive Officer of Bavarian Nordic. "On behalf of Bavarian Nordic, I want to express our gratitude to the PROSPECT investigators, patients and families who participated in this trial. While this is certainly not the desired outcome, we remain steadfast believers in the power of combination treatments, including immunotherapies, to transform the future of cancer therapies."

The contents of this announcement do not affect the Company’s expectations for the financial results for 2017.

About the PROSPECT study
PROSPECT was a global, randomized, double-blind, placebo-controlled Phase 3 study conducted under a Special Protocol Assessment (SPA) from the FDA. The objective of the study was to determine whether PROSTVAC alone or in combination with GM-CSF could prolong overall survival in men with asymptomatic or minimally symptomatic mCRPC. The study enrolled 1,297 patients at more than 200 sites in 15 countries.

About PROSTVAC
PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec, or "rilimogene") is a prostate specific antigen (PSA)-targeted immunotherapy candidate designed to enhance or stimulate the body’s immune response, specifically T cells that will home to and kill prostate cancer cells, altering the course of the disease and improving overall survival of patients with prostate cancer. PROSTVAC employs two poxviruses (vaccinia and fowlpox) in a prime-boost vaccine regimen. A robust data package has been established that includes 19 ongoing or completed clinical studies, comprising more than 2,000 patients, the majority of which have been actively treated with PROSTVAC, which has been generally well-tolerated.

PROSTVAC is being developed in collaboration with the National Cancer Institute under a Cooperative Research and Development Agreement.

Champions Oncology Reports Record Quarterly Revenue of $5 Million

On September 14, 2017 Champions Oncology, Inc. (Nasdaq: CSBR), engaged in the development of advanced technology solutions and services to personalize the development and use of oncology drugs, reported its financial results for the first quarter ended July 31, 2017 (Filing, Q2, Champions Oncology, 2017, SEP 14, 2017, View Source [SID1234520524]).

First Quarter and Recent Business Highlights:

•
Record quarterly revenue of $5.0 million, an increase of 37.1% year-over-year
•
Record Translational Oncology Services ("TOS") revenue of $4.6 million, an increase of 45.4% year-over-year
•
Engaged in a multi-year, strategic collaboration with AstraZeneca to develop models to be used in oncology R&D programs for breast and lung cancer
•
Collaborated with The Addario Lung Cancer Medical Institute ("ALCMI") to develop models in patients with ROS1 gene rearrangement
•
Reiterated expectations for fiscal year 2018 revenue growth of at least 20% over fiscal year 2017

Ronnie Morris, CEO of Champions, commented, "We delivered substantial increases in revenue and bookings for the first fiscal quarter and reduced our operating expenses both sequentially and year-over-year, reinforcing our confidence in achieving operating profitability for fiscal year 2018. Interest in our products and services drove quarterly revenues to more than $5 million for the first time in our history. We are rapidly approaching an inflection point in our business model where we expect the volume of solutions we sell to generate revenue that will soon exceed our total expenses, which are largely fixed. The first quarter included approximately $100,000 in non-recurring expenses related to the move to our new lab facility in Maryland, a move we expect will save approximately $1 million a year in a combination of fixed and variable costs based on current revenue levels beginning November 1, 2017. Excluding these one-time expenses and non-cash stock compensation expense, we would have realized income from operations for the quarter, a solid marker towards achieving sustained, similar quarterly result in the second half of fiscal 2018."

"Our multi-year collaboration with AstraZeneca and a research collaboration with Addario further expands the size, uniqueness and value of our TumorBank while also increasing our total addressable market to provide additional future growth opportunities," added Morris. "These relationships illustrate the breadth of our capabilities, the value we provide to our clients in their pre-clinical and clinical drug development research and the opportunities within our market."

Exhibit 99.1

Financial Results

For the first quarter of fiscal 2018, revenue increased 37.1% to $5 million, as compared to $3.7 million for the first quarter 2017. Total operating expenses for the first quarter fiscal 2018 and 2017 was $5.7 million and $6.2 million, respectively, a decrease of $500,000 or (8.7%).

For the first quarter of fiscal 2018, Champions reported a loss from operations of $619,000, including $564,000 in stock-based compensation, an improvement of $1.9 million or (75.5%) compared to the loss from operations of $2.5 million, inclusive of $1.1 million in stock-based compensation, in the first quarter of fiscal 2017.

For the first quarter of fiscal 2018 and 2017, Champions reported a loss from operations of $619,000 and $2.5 million, respectively, a decrease of $1.9 million or (75.5%). Excluding stock-based compensation of $564,000 and $1.1 million for the three months ended July 31, 2017 and 2016, respectively, Champions recognized a loss from operations of $55,000 and $1.4 million for first quarter 2018 and 2017, respectively.

The first quarter included approximately $100,000 in non-recurring expenses related to the new move to our new lab facility, a move the Company expects will save approximately $1 million a year off of current revenue levels beginning November 1, 2017. Excluding these one-time expenses and stock based compensation, the Company would have generated positive net income from operations.

Net cash used in operations was $1.9 million and $2.4 million for the three months ended July 31, 2017 and 2016, respectively, a decrease of $500,000 or (20.1%). The reduction in cash burn is the result of revenue growth and aggressive expense management; however, the total cash outflows for the quarter were mainly the result of fixed asset investments for our new lab facility along with a reduction in deferred revenue.

The Company ended the quarter with $430,000 of cash and cash equivalents. Despite the cash burn in the first quarter, the Company reiterates its position that it does not intend to raise capital in the equity market.

Translational Oncology Services (TOS) revenue was $4.6 million for the three months ended July 31, 2017 compared to and $3.2 million for the three months ended July 31, 2016, respectively, an increase of $1.4 million or 45.4%. The increase is due to continued strength in bookings from prior quarters, both in the number and size of the studies.

TOS cost of sales was $2.3 million for the three months ended July 31, 2017, an increase of $300,000, or 10.1%, compared to $2.0 million for the three months ended July 31, 2016. For the three months ended July 31, 2017 and 2016, gross margin for TOS was 50.9% and 35.1%, respectively. The increase in TOS cost of sales was due to an increase in the number and size of TOS studies. While gross margin often fluctuates quarter to quarter, resulting from timing differences between revenue and expense recognition, the improvement in gross margin was due to higher TOS revenue leveraged off the fixed cost component of the lab and effective management of the variable lab costs.

Personalized Oncology Services (POS) revenue was $439,000 and $511,000 for the three months ended July 31, 2017 and 2016, respectively, a decrease of $72,000 or (14.1%). The decrease is due mainly to a decrease in implant and drug panel revenue of $48,000 and $17,000, respectively.

Exhibit 99.1

POS cost of sales was $387,000 for the three months ended July 31, 2017, a decrease of $87,000, or (18.4%), compared to $474,000 for the three months ended July 31, 2016. For the three months ended July 31, 2017 and 2016, gross margin for POS was 11.8% and 7.2%, respectively. The improvement is attributed to the increase in higher margin sequencing revenue and aggressive management of lab-related costs.

Research and development expense was $1.1 million for the three months ended July 31, 2017, a decrease of $100,000, or (7.7%), compared to $1.2 million for the three months ended July 31, 2016. Sales and marketing expense for the three months ended July 31, 2017 was $683,000, a decrease of $242,000, or (26.2%), compared to $925,000 for the three months ended July 31, 2016. The decrease is mainly due to a reduction in stock based compensation expense. General and administrative expense was $1.2 million for the three months ended July 31, 2017, a decrease of $300,000 or (21.2%), compared to $1.5 million for the three months ended July 31, 2016. The decrease is mainly due to the decrease in stock based compensation expense.

Mirati Therapeutics Presents Positive Preliminary Data From On-Going Clinical Trials Of Sitravatinib In Non-Small Cell Lung Cancer

On September 14, 2017 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical stage targeted oncology biotechnology company, reported that positive preliminary data from two ongoing clinical trials of sitravatinib in non-small cell lung cancer (NSCLC) will be presented Friday, September 15th, 2017 at the IASLC 2017 Chicago Multidisciplinary Symposium in Thoracic Oncology (learn more at www.iaslc.org) (Filing, 8-K, Mirati, SEP 14, 2017, View Source [SID1234520523]).

Initial safety data and efficacy information will be presented from the ongoing Phase 2 study of sitravatinib in combination with nivolumab (OPDIVO) as a treatment for NSCLC patients with cancer progression following previous treatment with a checkpoint inhibitor. Additionally, a case study will be presented, documenting an objective response of a NSCLC patient with a CBL inactivating mutation. This was the first evaluable NSCLC patient harboring a CBL mutation treated in the ongoing Phase 1b study of sitravatinib as a single agent. In both clinical studies, sitravatinib alone and in combination with nivolumab was well tolerated with a manageable safety profile.

"For the majority of NSCLC patients who progress following checkpoint therapy, there is a need for new therapeutic options," said Charles M. Baum, M.D., Ph.D., President and Chief Executive Officer. "We are evaluating sitravatinib in combination with nivolumab in this checkpoint resistant population and are very encouraged by the responses observed, since responses would not be expected from re-treatment with a checkpoint inhibitor alone."

"In addition, in the single agent trial, the objective partial response is the first example of clinical activity in a patient with a CBL mutation. Inactivating mutations in CBL occur in approximately 1.5% of NSCLC patients and currently represent an unmet medical need."

Sitravatinib and Nivolumab Combination Study

Poster Presentation: Evidence of Clinical Activity of Sitravatinib in Combination with Nivolumab in NSCLC Patients Progressing on Prior Checkpoint Inhibitor Therapy

Clinical Trial: NCT02954991, A Phase 2 study evaluating the tolerability and clinical activity of sitravatinib in combination with nivolumab in patients with non-squamous NSCLC who have experienced progression of disease on or after treatment with checkpoint inhibitor therapy.

Presenter: Ticiana A. Leal, M.D.

This presentation provides a preliminary safety and efficacy update of the Phase 2 trial of sitravatinib in combination with nivolumab in NSCLC patients who have experienced progression of disease on or after treatment with checkpoint inhibitor therapy. In the efficacy data presented, 3 patients experienced a confirmed partial response out of 11 evaluable patients. Early safety data demonstrated an acceptable profile and manageable adverse events. Based on the data presented, the pre-defined criteria have been met for expansion from stage 1 to stage 2, which will enroll a combined total of 34 patients.

This study is designed to assess the potential of sitravatinib to inhibit several important immunosuppressive pathways that may be important in overcoming resistance to checkpoint inhibitor therapy.

Sitravatinib Single Agent Study

Poster Presentation: CBL Mutations as Potential Mediators of EGFR TKI Resistance Effectively Treated with Sitravatinib

Clinical Trial: NCT02219711, A Phase 1b study evaluating safety, PK, metabolism, PD and clinical activity of Sitravatinib in patients with advanced solid tumor malignancies

Presenter: Lyudmila A. Bazhenova. M.D.

The poster describes a case study of a NSCLC patient with a CBL mutation treated with sitravatinib. CBL loss of function mutations result in the increased activation of multiple oncogenic receptor tyrosine kinases (RTKs) in tumors, including PDGFRA, VEGFR2, KIT, Axl, and Mer. In preclinical models, sitravatinib has demonstrated the ability to potently inhibit these RTKs and induce tumor regression in NSCLC models harboring inactivating CBL mutations. In the case study presented, a heavily pre-treated NSCLC patient harboring an inactivating CBL mutation was treated with sitravatinib and demonstrated a confirmed partial response (PR) with a maximum decrease of 77% in target lesions. Early safety data is also provided; sitravatinib was well tolerated and the side effects observed were manageable. This trial is on-going and actively recruiting patients harboring CBL and other genetic mutations.

CBL mutations are present in 1.5% of NSCLC, 3.5% of melanoma, and 2% of cancers of unknown origin.

Both posters will be available on the Company’s website on the sitravatinib page, located in the Pipeline section, at: View Source

About Sitravatinib

Sitravatinib (MGCD-0516) is a spectrum-selective kinase inhibitor which potently inhibits receptor tyrosine kinases (RTKs) including RET, TAM family receptors (TYRO3, Axl, Mer), and split family receptors (VEGFR2, KIT). Sitravatinib is being evaluated as a single agent in a Phase 1b expansion trial enrolling patients that harbor RET, CHR4Q12, and CBL genetic mutations in NSCLC and other tumors.
As an immuno-oncology agent, sitravatinib is being tested in combination with BMS’ anti PD-1 checkpoint inhibitor nivolumab (OPDIVO) in NSCLC patients who have progressed after prior

treatment with a checkpoint inhibitor. Sitravatinib’s potent inhibition of TAM and split family receptors may help overcome resistance to checkpoint inhibitor therapy through targeted depletion of immunosuppressive Type 2 tumor associated macrophages, regulatory T cells and myeloid-derived suppressor cells and increasing antigen presentation capacity of dendritic cells in the tumor microenvironment.